Automated Bioprinter Using Aqueous Two-Phase Partitioning
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Solution Overview
Problem
Current tissue engineering methods face challenges in creating three-dimensional tissue constructs with spatial organization of cells, particularly in achieving organized cell placement, non-contact assembly, retention of cell viability, minimal use of toxic chemicals, and efficient layer-to-layer assembly without damaging forces or mutation-inducing radiation.
Innovation Solution
An automated mechanism using a three-axis motion control system and aqueous two-phase system (ATPS)-based bioprinting technology, which includes a cartridge with printing tips and a stabilized platform for precise cell placement and assembly, utilizing polymers like dextran and polyethylene glycol to form a partition for non-contact cell printing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If manual liquid handling tools are used for cell printing, then arbitrary shape printing is achieved, but manufacturing precision and reproducibility are limited
Solution Approach 1:
The patent replaces manual mechanical liquid handling tools with an automated bioprinting system that uses computer-controlled robotic arms or precision stages to position dispensing needles. This substitution enables programmable, reproducible cell placement with micrometer-level precision while maintaining the ability to print arbitrary patterns through software control.
Solution Approach 2:
The system allows dynamic adjustment of printing parameters including droplet volume, dispensing speed, needle position, and pattern geometry through software control. This enables the same hardware to achieve both high precision spatial organization and arbitrary shape printing by changing operational parameters rather than physical constraints.
2Manufacturing precision
If contact-based assembly methods are used, then cell placement control is improved, but cell viability is reduced due to damaging forces
Solution Approach 1:
The patent introduces a liquid medium (such as culture medium or specialized printing solution) as an intermediary between the dispensing system and cells. This intermediary allows cells to be suspended and transported without direct mechanical contact, enabling precise placement control through fluid dynamics while protecting cells from damaging mechanical forces.
Solution Approach 2:
The system uses pneumatic or hydraulic pressure control to dispense cell-containing droplets through fine-bore needles. By controlling pressure gradients and flow rates, the system achieves precise droplet placement and size control while maintaining gentle handling conditions that preserve cell viability throughout the printing process.
3Stability of the object's composition
If traditional hydrogel crosslinking is used, then structural stability is achieved, but mutation-inducing UV radiation is applied
Solution Approach 1:
The patent changes the crosslinking mechanism from UV-based photochemistry to alternative methods such as enzymatic crosslinking, chemical crosslinking at physiological pH, or physical crosslinking through temperature changes. These parameter changes eliminate exposure to mutation-inducing UV radiation while maintaining hydrogel structural stability through different molecular mechanisms.
Solution Approach 2:
The system replaces UV radiation-based crosslinking with alternative crosslinking approaches such as enzymatic reactions (e.g., transglutaminase-mediated crosslinking), chemical reactions using biocompatible crosslinkers, or physical crosslinking through controlled aggregation. These substitutions eliminate harmful radiation while achieving equivalent or superior structural stability.
4Reliability
If complex surface treatments are applied, then cell adhesion is improved, but device complexity and scale-up difficulty increase
Solution Approach 1:
The patent employs universal surface treatments or coatings that can be applied to various substrate materials (glass, plastic, metal) with consistent cell adhesion performance. This universal approach eliminates the need for material-specific complex surface treatments, reducing overall device complexity while maintaining reliable cell adhesion across different platform configurations for scale-up.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables reproducible, spatially organized cell placement and assembly with retained cell viability, minimizing toxic chemical use and avoiding damaging forces or radiation, facilitating efficient scale-up of three-dimensional tissue constructs.
Implementation Method 1
aqueous two-phase system (ATPS)-based bioprinting technology, which includes a cartridge with printing tips and a stabilized platform for precise cell placement and assembly, utilizing polymers like dextran and polyethylene glycol to form a partition for non-contact cell printing
Data Source
AI summary
The present invention are directed to a novel automated cell bioprinter and related methods for making three-dimensional tissue constructs with spatial organization of cells that provides: (i) organized cell placement and spatial assembly of multiple cell types in a reproducible manner (ii) direct and non-contact assembly of multiple cell types and/or cell layers without exerting damaging forces on the cells or tissues, (iii) retention of cell viability and functionality during assembly steps and long periods of culture, (iv) minimal use of harmful and toxic chemicals such as profuse amounts of mineral oil and buffer reagent, and (v) efficient layer-to-layer assembly of cell layers within the three-dimensional construct while (vi) avoiding the use of complicated surface treatments that prevents scale-up, and (vii) avoiding mutation-inducing radiations such as UV used to photocrosslink hydrogels.